Medical Hypotheses (2006) 67, 411–418

http://intl.elsevierhealth.com/journals/mehy

What frontotemporal dementia reveals about

the neurobiological basis of morality
Mario F. Mendez *

Departments of Neurology and Psychiatry and Biobehavioral Sciences, University of California

at Los Angeles, Neurobehavior Unit (691/116AF), V.A. Greater Los Angeles Healthcare Center,
11301 Wilshire Blvd, Los Angeles, CA 90073, USA

Received 1 January 2006; accepted 4 January 2006

Summary There is evidence that moral behavior is a product of evolution and an innate aspect of the human brain.
Functional magnetic resonance studies in normals, investigations of psychopaths, and acquired sociopathy from brain
lesions suggest a neurobiology of moral behavior. Reports of sociopathy among patients with frontotemporal dementia
(FTD) have provided a further opportunity to clarify the neurobiology of morality. They confirm a morality network that
includes the ventromedial frontal cortex, the orbitofrontal cortex, and the amygdalae. The right ventromedial region
is critical for the emotional tagging of moral situations, the orbitofrontal cortex responds to social cues and mitigates
impulsive reactions, and the amygdalae are necessary for threat detection and moral learning. Alterations in moral
behavior in FTD may result from a loss of the emotional label of moral dilemmas, coupled with disinhibited responses.
More investigations are needed to fully understand how the brain mediates moral or ethical behavior.
c 2006 Elsevier Ltd. All rights reserved.

Introduction and hypothesis ousy, a sense of fairness, feelings of reciprocity,

Morality is about ideals of human conduct such as
empathy, fairness, self-control, and duty [1].
These ideals promote social groups through moral
emotions such as guilt, gratitude, compassion,
xenophobia, and outrage at unfair treatment. Much
evidence indicates that moral ideals and emotions
are the products of evolutionary pressures on social
animals [1,2]. Studies with apes and other nonhu-
man animals describe moral behavior guided by
moral emotions such as empathy, gratitude, jeal-
* Tel.: +1 310 478 3711x42696; fax: +1 310 268 4181.
E-mail address: mmendez@UCLA.edu.
righteousness, and consolation [2–4].
If much of morality is innate and a product of
evolution, what is its neurobiological basis? Investi-
gations are beginning to clarify the brain substrates
of moral behavior. Functional magnetic resonance
imaging (fMRI) studies in normals exposed to moral
pictures implicate frontotemporal regions in moral
judgments [2,3]. These studies suggest a ‘‘morality
network’’ that particularly comprises the right ven-
tromedial (VM) frontal cortex, the orbitofrontal
(OF) cortex, and the amygdalae [2,3,5]. The VM
frontal region, or the lower inner aspect of the
frontal lobes, attaches socioemotional value to
environmental stimuli and biases moral judgments.
The OF cortex, or the inferior underbelly of the


0306-9877/$ - see front matter c 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2006.01.048
412
frontal lobes, processes social cues and inhibits
immediate and amygdalar responses [6]. The amy-
gdalae, located in the adjacent anteromedial tem-
poral lobes, mediate the response to threat and
aversive social and moral learning [7]. fMRI hypoac-
tivity in the amygdalae may represent the neural
correlate of psychopathic behavior and overactiv-
ity may underlie social fear [8]. Finally, in humans,
this morality network can be overridden by dorso-
lateral (DL) frontal ‘‘executive’’ processes [5].
In addition to fMRI studies in normals, the study
of patients with brain disease can significantly con-
tribute to our understanding of the neurobiology of
morality. Focal strokes and tumors and develop-
mental disorders such as autism have also impli-
cated the medial and inferior frontal and anterior
temporal/amygdalar regions. There is an additional
slow, more insidious neurodegeneration of these
moral regions of the brain. Frontotemporal demen-
tia (FTD) gradually alters moral behavior and allows
a specific examination of the relationship between
neuropathology and moral behavior. Alterations in
moral behavior in FTD are, therefore, another win-
dow to the organization of moral behavior in the
brain. The hypothesis proposed here is that altera-
tions in moral behavior in FTD result from a loss of
the emotional value of moral dilemmas, coupled
with disinhibited responses.
Frontotemporal dementia
FTD is a progressive neurodegenerative disorder
that affects the frontal lobes, temporal lobes, or
Figure 1 2-[F-18] fluoro-D-glucose positron emission tomography (PET) images in the horizontal plane of a patient
with frontotemporal dementia. The scans are in the resting state and show prominent loss of metabolic activity in the
frontal and anterior temporal regions.
Mendez
both (see Fig. 1). The transgression of social norms
is a core diagnostic feature of FTD. Another core
behavioral feature is ‘‘emotional blunting,’’ a term
that includes a loss of empathy or appreciation of
the feelings of others [9]. Patients with FTD have
a loss of insight for their behavior and its conse-
quences. Together, these core behavioral features
of FTD suggest a disturbance in the neurobiological
substrate of morality [10].
FTD patients manifest violations of moral rules
or norms early in their disease [9]. These patients
appear self-centered and do not respond to the
needs of others or even acknowledge them. Antiso-
cial behavior, a measure of ‘‘immoral behavior,’’
occurs in more than half of patients with FTD
[11]. Investigators have described FTD patients
with stealing and shoplifting [10,12,13], inappro-
priate sexual behavior [14,15], physical aggression
and acts of violence [12,15], frequent traffic viola-
tions and hit-and-run accidents [16], and even
pedophilia [10] (see Table 1).
A review of the literature suggests different
mechanisms that could account for defective moral
judgment in FTD. It could result from a loss of the
knowledge of right or wrong or the development of
a ‘‘moral agnosia’’. It could result from an alter-
ation in the ability to reason logically as applied
to moral judgments. It could result from deficits
in person recognition, empathy, theory of mind,
emotional responsiveness to moral dilemmas, or a
general ‘‘somatic marker’’. In addition, there
may be a contribution from an inability to control
immediate impulses. This article examines these
possibilities in FTD after first defining the neurobi-
What frontotemporal dementia reveals about the neurobiological basis of morality
Table 1 Sociopathic acts among 16 patients with
frontotemporal dementia
Number Type
3 Unsolicited sexual approach or touching
3 Traffic violations including hit-and-run
accidents
2 Physical assaults
1 Shoplifting
1 Deliberate non-payment of bills
1 Pedophilia
1 Indecent exposure in public
1 Urination in inappropriate public places
1 Stealing food
1 Eating food in grocery store stalls
1 Breaking and entering into others’ homes
From Ref. [11].
ology of developmental sociopathy in psychopaths
and of acquired sociopathy from brain lesions.
The neurobiological basis of psychopaths
Psychopaths are egocentric, lack empathy or social
emotions, and commit antisocial acts [17]. They
engage in deception, lying, manipulation, intimida-
tion, and violence in order to control others for
personal gain. As children, future psychopaths
may torture small animals, set fires, commit van-
dalism, and be incorrigible to punishment. As
adults, they can reason morally but have difficulty
distinguishing between victim-based and social
rule-based transgressions [17]. The most specific
characteristics of psychopaths are the presence
of instrumental (predatory, goal-directed, cold-
blooded) aggression and the absence of significant
autonomic nervous system arousal to socioemo-
tional stimuli [17]. Psychopaths show little alter-
ation in heart rate, blood pressure, respirations,
or galvanic skin responses when they are subjected
to fear, stress, or unpleasant pictures and, conse-
quently, seek constant stimulation [18–20]. Fur-
thermore, antisocial persons with reduced
autonomic arousal during social stressors have re-
duced prefrontal gray matter volume [21].
There is a high incidence of frontotemporal
changes among violent offenders [22]. Positron
emission tomography (PET) studies have shown fron-
tal or anterior temporal hypometabolism in murder-
ers pleading not guilty by reason of insanity and in
violent psychiatric inpatients [19,23–26]. In one
study [27], 20 (64.5%) of 31 murderers had specific
neurological diagnoses, including mental retarda-
tion, cerebral palsy, epilepsy, alcoholic dementia,
413
brain injury, and others. On neurological examina-
tions, the 31 murderers showed frequent frontal
(20; 64.5%) or temporal (9; 29%) deficits. In another
study [26], 20% of violent males imprisoned in a max-
imum-security mental hospital had focal temporal
abnormalities on electroencephalograms and 41%
had temporal lobe changes on neuroimaging, com-
pared to 2.4% and 6.7% for the nonviolent group,
respectively. Single photon emission tomography
has shown a relationship of psychopathological fea-
tures with frontotemporal hypoperfusion [28], and
magnetic resonance spectroscopy has shown a rela-
tionship of violent behavior with low frontal neuro-
nal density and high-energy metabolism [29].
Additionally, on neuropsychological measures,
executive functions from the DL frontal lobes are
frequently impaired in institutionalized psycho-
paths, antisocial individuals, and violent psychiatric
inpatients [29–32]. This DL frontal dysfunction may
be more related to degree of success rather than to
the presence of psychopathy itself [33]. Some inves-
tigators suggest that, compared to DL deficits, OF
deficits are more consistently present among psy-
chopaths [17,34].
In addition to frontal changes [32], psychopaths
are deficient in some amygdalar functions [17,22].
Whereas impulsive reactive aggression may follow
the OF damage, the more specific instrumental
aggression with impaired processing of fear and
distress cues, may follow amygdalar damage [17].
The amygdalae play a role in averse conditioning
(punishment) and instrumental learning (especially
passive avoidance learning), and the retrieval of
socially relevant knowledge, such as facial trust-
worthiness or approachability [7]. Psychopaths
are impaired in these amygdalar functions and,
along with autonomic hyporesponsivity to aversive
stimuli such as social criticism, lack moral sociali-
zation and fail to develop moral behavior [17].
Acquired sociopathy
Acquired sociopathy refers to the behavior of per-
sons who, after acquired brain lesions, violate so-
cial and emotional norms and rules. Amygdalar
lesions are not as related to acquired sociopathy
as are VM and OF lesions. The amygdalae modulate
reactive, emotional aggression and the brain stem-
hypothalamus threat response system [17], and
amygdalar lesions may result in the Klüver–Bucy
syndrome with placidity, rather than a more perva-
sive loss of moral behavior. Compared to later le-
sions, VM or OF lesions acquired before age 16
months may lead to more severe antisocial behav-
ior and repeated failure to respond to interventions
414
[35]. Like psychopaths, those with acquired sociop-
athy from brain lesions have autonomic hypore-
sponsivity, especially in response to social stimuli
[21,36,37], but, unlike psychopaths, they do not
have the constant need for stimulation, grandios-
ity, deceitfulness, manipulativeness, and instru-
mental aggression [38]. Moreover, the autonomic
hyporesponsivity is more general in acquired soci-
opathy and more selective for fearful and sad
expressions in psychopaths [39,40].
Lesion studies suggest that the VM frontal cortex,
especially on the right, is critical to socioemotional
decision-making, emotional functioning, and social
behavior [41,42]. The VM frontal cortex, which has
rich interconnections with limbic structures, guides
moral and social behavior by re-experiencing previ-
ously learned somatic and emotional responses in
novel social situations [37,43–45]. Patients with
VM frontal lesions have a general dampening of
emotional experience, autonomic responsivity,
and insensitivity to future consequences or out-
comes of their actions [36,37,42–47]. Yet, they
are aware of their actions and possess the necessary
knowledge to anticipate future outcomes [48].
The OF evaluates socioemotional cues, sup-
presses impulsive and aberrant responses, and par-
ticipates in response reversal learning [38]. OF
damage impairs the use of feedback from aversive
socioemotional cues, such as angry expressions or
punishment; this feedback is necessary for judging
the appropriateness of responses and for controlling
impulsive reactions [6,35,38,49–51]. In addition to
simple motor impulsivity, patients with OF lesions
have reactive, aggressive dyscontrol with violent
or angry emotional outbursts [49,52–54]. Finally,
the OF is necessary for changing a response to a stim-
ulus when the reinforcement contingencies change.
Morality and FTD
FTD patients resemble those with acquired sociop-
athy much more than they do psychopaths. FTD pa-
tients are emotionally shallow and autonomically
hyporesponsive, but they lack deliberate deceitful-
ness, instrumental aggression, or the need for con-
stant stimulation [9,15,55]. Several mechanisms
could explain the moral transgressions found
among patients with FTD (see Table 2).
One possibility is that patients with FTD loss moral
knowledge or develop a ‘‘moral agnosia.’’ Similar to
the loss of semantic knowledge in the related seman-
tic dementia syndrome [9], those with FTD might
lose semantic knowledge for moral rules and norms.
In order to evaluate for the presence of moral agno-
sia, one study administered a moral behavior inven-
Mendez
Table 2 Moral behavior inventory
How wrong is it if you:
1 – Not wrong 2 – Mildly wrong 3 – Moderately
wrong 4 – Severely wrong
_____ Fail to keep minor promises
_____ Take the last seat on a crowded bus
_____ Sell someone a defective car
_____ Drive after having one drink
_____ Cut in line when in a hurry
_____ Don’t give blood during blood drives
_____ Are mean to someone you don’t like
_____ Say a white lie to get a reduced fare
_____ Drive out the homeless from your community
_____ Always let others pay at a restaurant
_____ Not help someone pick up their dropped papers
_____ Keep over-change at a store
_____ Not offer to help after an accident
_____ Ignore a hungry stranger
_____ Fail to vote in minor elections
_____ Keep money found on the ground
_____ Temporarily park in a handicap spot
_____ Cut off drivers on the freeway
_____ Take the largest piece of a pie
_____ Falsely get out of jury duty
_____ Ask others do some of your homework
_____ Take credit for others’ work
_____ Refuse to help people who don’t deserve it
_____ Get more time off than your co-workers
From Ref. [10]. This questionnaire presents acts for you to
evaluate in terms of right or wrong. Please answer to the
best of your ability. Choose 1 if the item seems not wrong.
Choose 4 if the item seems severely wrong. Use 2 and 3 for
in-between degrees of wrongness.
tory to patients with FTD (see Table 3) [10]. This
inventory queried patients for their responses on a
Likert Scale to common issues requiring contempo-
rary moral knowledge. In comparison to AD patients
and normal controls, the FTD patients had retained
knowledge of moral rules and conventional norms.
They did not display deficits in moral semantic mem-
ory, and they knew the conventional right and wrong
answers to moral questions.
Violations of moral rules may result from impair-
ment in the ability to make rational, non-emotion-
Table 3 Possible mechanisms for disturbed moral
behavior in FTD
Loss of moral knowledge or ‘‘moral agnosia’’
Defective non-emotional moral reasoning
Impaired person recognition network
Loss of cognitive or emotional empathy
Abnormal theory of mind
Defective emotional moral reasoning
Abnormal somatic marker
Poor impulse control
What frontotemporal dementia reveals about the neurobiological basis of morality
based moral judgments [5]. The ability to apply
non-emotional moral reasoning requires DL frontal
executive abilities. Greene et al. [56] used func-
tional MRI data to indicate that DL frontal pro-
cesses, such as working memory and abstract
thought, drive reflective moral reasoning. Prior re-
search, however, has shown that FTD patients can
reason normally when the dilemmas or tasks involve
‘‘impersonal’’ or non-emotional decisions [10].
Disturbances along a person recognition network
in the right frontotemporal region may affect moral
behavior [57,58]. Semantic information appears to
be organized into an ‘‘animate’’ category and a
‘‘person-specific’’ discrete region in the right ante-
rior temporal region and may include a mechanism
for ‘‘humanness’’ [57,59–63]. Right anterior tem-
poral lesions or dementia can disproportionately im-
pair access to living things, a person-specific
knowledge from faces, facial emotions, voice, and
other modalities [57,49,61,64]. FTD studies have
shown decreased recognition of facial emotions,
especially negative emotions, with right temporal
(amygdala) and OF involvement and decreased
detection of ‘‘humanness’’ with right temporal
FTD [55,57,63,65,66]. Disturbances along this per-
son recognition network, however, would not ex-
plain most victimless sociopathic acts and could
not account for a more general alteration in moral
behavior in FTD.
Morality involves empathy, or the ability to iden-
tify and understand others’ feelings and emotions.
Empathy has cognitive components such as perspec-
tive taking and emotional components such as emo-
tional contagion. People understand the mental and
emotional states of others by representations that
simulate the same mental and emotional state in
themselves [67]. FTD patients with predominant
right hemisphere involvement develop personality
changes consistent with a loss of empathy for other
human beings [14,68,69]. Studies of FTD patients
have also shown decreased cognitive empathy (per-
spective taking) and decreased agreeableness with
right OF involvement and interpersonal coldness or
decreased emotional empathy with anterior tempo-
ral involvement [70–73]. Similar to disturbances in
person recognition, the presence of decreased
empathy, whether cognitive or emotional, cannot
entirely explain sociopathic acts that do not involve
other individuals. Loss of moral behavior in FTD is
even more general than their loss of empathy.
Theory of mind (ToM) is the ability of individuals
to attribute motivations, affects, and thoughts to
others [74,75]. Deficits in ToM are characteristic
of autism. In some situations, ToM can also be dis-
turbed in those with VM, OF, or DL frontal and amy-
gdalar lesions, especially on the right [75–77]. The
415
exact nature of the necessary lesion, however, is
unclear since extensive damage to the VM frontal
lobes bilaterally can spare most ToM functions
[78]. ToM may be defective in some individuals
with FTD [79–82]. They may be particularly unable
to read the feelings and emotions (‘‘affective
ToM’’) of others as evident on irony and faux pas
tasks [82,83]. Both impaired affective ToM and loss
of empathy suggest a problem in the emotional
labeling of experience in patients with FTD.
Violations of moral rules may result from damage
to automatic, emotionally-based moral judgments
[1–3]. Rather than deliberate and overtly rational,
most moral judgments are actually rapid, involun-
tary, emotional and intuitive, and, when violated,
elicit negative emotional feelings [5,84]. Greene
et al. [56] showed that socioemotional dispositions,
such as discomfort at the prospect of causing direct
harm to a specific person, drive automatic moral re-
sponses and one associated with fMRI activity in the
VM frontal lobes [5,56]. Insensitivity to personal
moral dilemmas results when this VM system is dis-
turbed from focal lesions [43,44,48]. In a unique
study, FTD patients were impaired in their ability
to immediately respond to emotionally-based moral
dilemmas, compared to AD patients and normal
controls [10]. The FTD patients solved moral dilem-
mas in an impersonal deliberate fashion. These
findings again point to a disturbance of automatic
emotional ‘‘tagging’’ of environmental situations.
Normal individuals reactivate previously learned
and felt somatic or physiological reactions to prior
social situations in response to new social situa-
tions [45]. When this ‘‘Somatic Marker’’ system is
disturbed, as in VM damage, there is insensitivity
to potentially negative consequences despite re-
tained knowledge of social rules and potential out-
comes [44,45,48]. The FTD patients with
sociopathy resemble those with acquired VM le-
sions in their insensitivity to the potential conse-
quences of their acts despite retained knowledge
of potential outcomes [11]. Disturbances in the so-
matic marker system is yet another reflection of
impaired emotional reactivity evident in the loss
of affective ToM and of emotional moral decision-
making. This emotional disconnection is critical ap-
pears alterations in moral behavior in FTD.
A final and somewhat distinct consideration is the
loss of control, or impulsivity, that often accompa-
nies OF injury. This can lead to impulsive theft,
sexual touching, and even reactive aggression.
Although FTD patients resemble those with OF dam-
age in their tendency to react impulsively in tempt-
ing situations, many of their immoral acts, such as
nonpayment of bills, lack of emotional support,
some traffic violations, and others (See Table 1),
416
are not entirely impulsive in nature. Nevertheless,
there is a strong correlation between measures of
OF dysfunction and poor impulse control with socio-
pathic behavior in FTD [11]. Moreover, FTD patients
may be deficient in their ability to choose among
behavioral alternatives based on inferences about
positive or negative outcomes and changes in contin-
gencies [50,51].
Conclusions
FTD patients violate social norms and conventions
and behave ‘‘immorally.’’ Some FTD patients have
committed crimes and have even been arrested
[11,12,15]. They may know right and wrong and
understand the nature of their acts sufficiently
that, under most guidelines, they would not qualify
for ‘‘not guilty by reason of insanity.’’ Since 1984,
the federal insanity defense requires the defendant
to prove, by ‘‘clear and convincing evidence,’’ that
‘‘at the time of the commission of the acts consti-
tuting the offense, the defendant, as a result of a
severe mental disease or defect, was unable to
appreciate the nature and quality or the wrongful-
ness of his acts’’ (18 U.S.C. Section 17). Under these
guidelines, FTD patients, whose focal brain deteri-
oration results in unlawful behavior, would be held
culpable, illustrating one important societal reason
for clarifying the neurobiology of moral behavior.
FTD is a model to understand morality and the
brain. FTD patient retain knowledge for moral
behavior and the ability to make ‘‘rational’’ moral
judgments. FTD patients can commit sociopathic
acts even without victims, hence, impaired person
recognition, empathy or theory of mind would not
suffice to explain their behavior. It is more consis-
tent with decreased emotional moral judgments
and impaired somatic markers due to decreased
emotional correlates, which are coupled with
insufficient control of impulsivity. These changes,
which are consistent with neuropathology in the
VM and contiguous OF regions of the frontal lobes,
can explain the loss of moral behavior and the pres-
ence of sociopathic acts observed among patients
with FTD. These findings have implications for
understanding the organization of our moral sense
in the brain.
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